IP Library › Granted Patent US 10,605,734
Granted Patent B2
US 10,605,734 · App. 14/779,532 · Granted Mar 31, 2020

Systems and methods for genetic sequencing

Inventors: William M. Lafferty (Encinitas, CA); Jonathan M. Rothberg (Guilford, CT); Keith G. Fife (Palo Alto, CA)
Assignee: LIFE TECHNOLOGIES CORPORATION
G01N21/648C12Q1/6874G01N21/6454G01N2021/6441
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Quick Facts
Patent No.
US 10,605,734
App. No.
14/779,532
Granted
Mar 31, 2020
Kind
B2
Abstract

A device including a transparent layer defining a surface exposed to a flow volume and to secure a target polynucleotide template and a detector structure secured to the transparent layer and including a plurality of detectors to detect a signal emitted during nucleotide incorporation along the target polynucleotide template.

Claims (28)

1. A device comprising:

a transparent layer defining a surface exposed to a flow volume and including a plurality of regions, each region to secure a target polynucleotide template; and

a detector structure in optical communication with the transparent layer and including a plurality of detectors configured to detect a fluorescent signal emitted during nucleotide incorporation during template-dependent nucleic acid synthesis, wherein the detector structure includes a plurality of pixels, each pixel of the plurality of pixels including a set of detectors of the plurality of detectors, the set of detectors disposed in a semiconductor structure, each detector of the set of detectors disposed at a different depth within the semiconductor structure when viewed in cross-section, a detector of the set of detectors overlapping another detector of the set of detectors when viewed in a plan view; wherein a pixel is in optical communication with a region;

wherein the set of detectors within the semiconductor structure include a p-type substrate, a deep n-type implant, a shallow n-type implant, and a p-type implant disposed over the shallow n-type implant.

2. The device of claim 1 , wherein the set of detectors includes at least two detectors.

3. The device of claim 2 , wherein each pixel includes at least three detectors.

4. The device of claim 3 , wherein each pixel includes at least four detectors.

5. The device of claim 1 , wherein the transparent layer includes an energy propagation layer.

6. The device of claim 1 , further comprising an energy propagation layer disposed between the transparent layer and the detector structure.

7. The device of claim 6 , wherein the energy propagation layer includes a total internal reflection layer.

8. The device of claim 6 , further comprising an energy emitting component to provide energy to the energy propagation layer.

9. The device of claim 1 , further comprising a separator structure extending from the detector structure toward the transparent layer, the separator structure opaque to the fluorescent signal.

10. The device of claim 1 , further comprising a filter layer disposed between the device structure and the transparent layer.

11. The device of claim 10 , wherein the filter layer is configured to limit transmission of excitation energy.

12. The device of claim 10 , wherein the filter layer is configured to permit the transmission of a wavelength spectrum associated with a dye.

13. The device of claim 1 , further comprising a well structure defining wells disposed on the transparent layer opposite the detector structure.

14. The device of claim 1 , further comprising a pad structure disposed on the transparent layer opposite the detector structure.

15. The device of claim 1 , further comprising a lid, the flow volume defined between the lid and the transparent layer.

16. The device of claim 1 , wherein the transparent layer comprises an electrode.

17. An apparatus comprising:

a transparent layer defining a surface exposed to a flow volume and including a plurality of surface wells, each surface well to secure a target polynucleotide template, the plurality of wells defined by a well structure;

an energy propagation layer disposed opposite the surface of the transparent layer to propagate photonic energy along a path parallel to the surface;

an excitation filter layer secured to the energy propagation layer opposite the transparent layer, the excitation filter layer opaque to the photonic energy;

a microlens layer secured between the excitation filter layer and the detector structure, the microlens layer including a plurality of microlenses, each microlens of the plurality of microlenses aligned between a well of the plurality of wells and a pixel of the plurality of pixels; and

a detector structure secured to the microlens layer opposite the energy propagation layer, the detector structure defining a plurality of pixels, each pixel including a plurality of detectors, each pixel of the plurality of pixels uniquely optically associated with a well of the plurality of wells, the plurality of detectors disposed in a semiconductor structure, each detector of the plurality of detectors disposed at a different depth within the semiconductor structure when viewed in cross-section, a detector of the plurality of detectors overlapping another detector of the plurality of detectors when viewed in a plan view, wherein the set of detectors in the semiconductor structure include a p-type substrate, a deep n-type implant, a shallow n-type implant, and a p-type implant disposed over the shallow n-type implant.

18. The apparatus of claim 17 , wherein each pixel includes at least two detectors.

19. The device of claim 1 , wherein the semiconductor structure comprises a silicon substrate, and wherein the each pixel comprises a set of oppositely charged implants disposed in the silicon substrate.

20. The device of claim 1 , further comprising circuitry associated with each pixel to selectively detect charge within layers forming the plurality of detectors.

Assignments (1)
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Jan 29, 2019
From: LAFFERTY, WILLIAM M.; ROTHBERG, JONATHAN M.; FIFE, KEITH G.
To: LIFE TECHNOLOGIES CORPORATION
Reel/Frame 048164/0216 →
Continuity (3)
Provisional Application 61835428 · Jun 14, 2013
Provisional Application 61808105 · Apr 3, 2013
Related Publication 20160047747A1 · Feb 18, 2016
Cited By (1)
US 12,227,775